Hypermobile EDS in Adults HowardP.Levy,MD,PhD

AssociateProfessor,JohnsHopkinsUniversity

September8,2017

2017EDSGlobalLearningConferenceLasVegas,NV

Disclosures

• Nofinancialorotherconflictsofinterest

Agenda

EnglandandAmericaaretwocountriesseparatedbyacommonlanguage.-GeorgeBernardShaw,orOscarWilde,ornobodyMe:“ShouldIfocusonnuancesofthenewdiagnosSccriteriaoronmanagement?”Lara:“Yes”

Revised Diagnos;c Criteria: Why • GeneScheterogeneity• “Tighter”criteriashouldhelpfindtheunderlyinggene(s)

• Otherdiagnosesmayexist• Managementmaydiffer• Don’tendthe“diagnosScodyssey”prematurely

• Risk(further)lossofcredibilityifcriteriaaretoolax

Revised Diagnos;c Criteria • PrioriSzespecificityoversensiSvity• SomeEDScasesmaybefalselyexcluded• LessriskoffalselyincludingthosewithoutEDS

• HypermobilitySpectrumDisorder(HSD)• Not“normal”butnotclearlyhEDS

• Expectfurtherrevisionsa`ergenesarefound• Some(notall)HSDeventuallyreclassifiedasEDS

Diagnos;c Criteria: Excluded Features Toonon-specificorinsufficientlystudied•  Sleepdisturbance&faSgue•  PosturalorthostaSctachycardia•  FuncSonalgastrointesSnaldisorders•  Dysautonomia•  Anxiety&depression•  Chiari&tetheredcord•  MastcelldysfuncSon

Diagnos;c Criteria: Defining hEDS hEDS is a heritable connec;ve ;ssue disorder • Heritable• Familyhistory

• ConnecSveSssue• Generalizedjointhypermobility• SystemicconnecSveSssueinvolvement

• Disorder• FuncSonalmusculoskeletalconsequences

Diagnos;c Criteria: Defining hEDS hEDS is a heritable connec;ve ;ssue disorder Diagnosisrequiresall3:• GeneralizedJointHypermobility(connecSveSssue)• Atleast2of…• SystemicconnecSveSssuemanifestaSons(connecSveSssue)• PosiSvefamilyhistoryina1stdegreerelaSve(heritable)• MusculoskeletalcomplicaSons(disorder)

• Exclusionofotherdiagnoses

hips://www.ehlers-danlos.com/heds-diagnosSc-checklist/

Generalized Joint Hypermobility

Generalized Joint Hypermobility Beightonscore--Standardizedandstrictcriteria:• Palm&forearmresSngflat&elbowflexed90°.Does5thmetacarpal-phalangealjointextend>90°?• Armoutstretched&handpronated.Canthumbcanbepassivelytouchedtotheforearm?• Armtoside&handsupine.Doeselbowextend>10°(ideallyusegoniometer)?• Standingwithkneeslocked.Doeskneeextend>10°(ideallyusegoniometer)?• Standingwithkneeslocked&feettogether.Canbothtotalpalmstouchflattofloorjustinfrontofthefeet?

Generalized Joint Hypermobility

Beightonscore• Standardizedandstrictcriteria• Age-relatedcut-offs

• Veryyoung?• Late40s/early50s?

Pre-puberty Pubertytoage50 Beyondage50

6 5 4

Generalized Joint Hypermobility IfBeightonscorenotfullyassessedor1belowcut-off• SubjecSvejointexam?• ToosubjecSvetobeincludedatthispoint

• 5PointQuesSonnaire•  2ormoreoutof5“yes”•  80–90%specific(10-20%falseposiSve)• Notvalidatedinchildren

WesSllneedbeierassessmenttools

Systemic Connec;ve Tissue Manifesta;ons

Systemic Connec;ve Tissue Manifesta;ons • Unusuallyso`/velvetyskin• SubjecSve;highthresholdrecommended

• Mildskinhyperextensibility• Volarforearm• 1.5-2cm

• Unexplainedstriae• Nosignificantweightgain/loss• Adolescents,menorprepubertalwomen

Systemic Connec;ve Tissue Manifesta;ons • RecurrentormulSpleabdominalhernias• Nothiatalhernia

• Atrophicscarring• Atleasttwosites• MilderthancEDS

• Pelvicprolapse• Children,menornever-pregnantwomen• Withoutobesityorothercause

Systemic Connec;ve Tissue Manifesta;ons

• Dentalcrowdingandhighornarrowpalate• Includeshistoricalifcorrected• MustbebothcrowdingANDhighornarrowpalate

• Totalof12possible• 5ormoretobeconsideredposiSve• Expectfurtherrevisionsa`ergenesarefound

Posi;ve Family History

• 1stdegreerelaSvesonly• Autosomaldominantinheritance

• MustindependentlymeetcurrentcriteriaforhEDS• Priorcriteriadon’tcount• HSDdoesn’tcount

Jointlaxity(andmanyotherthings)canruninthefamilywithoutbeinghEDS.

Musculoskeletal Complica;ons Atleastoneof…• Dailypainin2ormorelimbs(arm/leg)for3+months• Chronic,widespreadpainfor3+months• Recurrent,atraumaScjointdislocaSonsorfrankinstability• 3+dislocaSonsinthesamejointor2+dislocaSonsin2differentjoints• Medicallyconfirmedjointinstabilityat2+sites• Instability/dislocaSoniscommon&normala`ertrauma• DislocaSon=boneoutofnormalposiSonsufficientlyseveretolimitmoSonofthejointandrequiringmanualreducSon

Exclusion of Other Diagnoses • SkinfragilityàothertypesofEDS• OtherheritableandacquiredconnecSveSssuedisorders• IfautoimmunerheumatologiccondiSon(e.g.lupus,rheumatoidarthriSs),donotcountpainorjointinstabilitytowardshEDSdiagnosis

• OthercondiSonsthatmaycauseconnecSveSssuelaxityand/orreducedmuscletone

My Prac;ce: March 1 – August 31

EDS39%

NotEDS11%

NotHCTD44%

OtherHCTD6%

2015

EDS25%

NotEDS25%

NotHCTD50%

2016

EDS30%

HSD32%

NotHCTD38%

2017

My Prac;ce: March 1 – August 31 Prior years re-interpreted

EDS32%

NotEDS18%

NotHCTD47%

OtherHCTD3%

2015-16Original

EDS25%

HSD22%

Uncertain3%

NotHCTD47%

OtherHCTD3%

2015-16Re-interpreted

My Prac;ce: March 1 – August 31 Prior years re-interpreted

EDS25%

HSD22%

Uncertain3%

NotHCTD47%

OtherHCTD3%

2015-16Re-interpretedEDS

Original Re-interpreted Changes

Hypermobile 91% 77% ToHSD

Classical 9% 0% TohEDS

HSD 0% 18% FromhEDS

NotHCTD 0% 5% hEDStoPsoriaScArthriSs

My Prac;ce: March 1 – August 31 Prior years re-interpreted

EDS25%

HSD22%

Uncertain3%

NotHCTD47%

OtherHCTD3%

2015-16Re-interpretedHSD

Original Re-interpreted Comment

NotEDS 71% 0% ToHSD&Uncertain

HSD 0% 88% Fromallothers

hEDS 24% 0% ToHSD

NotHCTD 6% 0% ToHSD

Uncertain 0% 12% FromNotEDS

My Prac;ce: March 1 – August 31 3 Years Pooled

EDS26%

HSD26%Uncertain

2%

NotHCTD44%

OtherHCTD2%

2015-2017Pooled

NotHCTD

Autoimmune/Rheumatologic 9%

Neuromuscular(includingmitochondrial) 18%

OsteoarthriSs/SpinalStenosis 16%

Painorother 58%

Natural History/Manifesta;ons: 3 Phases Highlyvariable;nottrueforeveryone• Hypermobility• Laxity&instabilityexceedspain.SomefaSgue.

• Pain• Increasingpain,“fibromyalgia,”increasingfaSgue.• Othersystemicinvolvement.

• SSffness• Reducedmobility,furtherincreaseinpain&faSgue.

Natural History/Manifesta;ons: Pain Acute&Chronic• NocicepSve(affectedmuscles,joints,&connecSveSssue)• Neuropathic• PotenSalcauses:• Muscle/tendon/connecSveSssuespasm• Traumaduetojointinstability• Nerveentrapment• OsteoarthriSs• CentralsensiSzaSon&generalizedhyperalgesia

Natural History/Manifesta;ons: Skin & Fascia MuchmilderthanothertypesofEDS• So`• Hyperextensible• Fragile• Atrophicscars• Stretchmarks• CSFleaks?(literatureismixed)• Hernias

Natural History/Manifesta;ons: Fa;gue • Physical&mental• CanbedebilitaSng• ComplexinteracSonswith• Pain• Sleepdisturbance• Dysautonomia• MedicaSons&allergies• Psychologicaldistress• OthercomplicaSons

Natural History/Manifesta;ons: Heart & GI

Cardiovascular• MildaorScrootdilaSon• POTS,NeurallyMediatedHypotension,OrthostaScIntolerance• Mitralvalveprolapse?(literatureismixed)

GastrointesSnal• GERD,heartburn,bloaSng• Abdominalpain• IBS,diarrhea,consSpaSon,defecatorydysfuncSon

Natural History/Manifesta;ons: Headache • Migraines• Tensionheadaches• Cervical&craniocervicalinstability?CSFleak?• POTS/NMH• MedicaSons&reboundheadache• TemporomandibularJointDysfuncSon(TMD)• WithrelatedsecondarycomplicaSons

Natural History/Manifesta;ons: Pregnancy • Increasedlaxity• Rapidlabor• VariablesystemicmanifestaSons(pain,GI,etc)• 40%worse,47%stable,13%improved

• Nodocumentedeffecton• Pretermbirthormiscarriage• FerSlity• Bleeding• Outcomesofvaginalvs.Caesareandelivery

Natural History/Manifesta;ons: Psychiatric • Depression,anxiety&affecSvedisorder• Lowself-confidence• NegaSvethinking• HopelessnessanddesperaSon• Avoidancebehavior• ExacerbaSonofdysfuncSonanddisability• MarginalizaSon• Resentment,distrust,andhosSlitybetweenpaSent,family,andhealthcareteam

Management • I’mprobablyovermyalloiedSmealready.• NothingdrasScallychangedsincelastyear.• Seehip://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31538/full• Aiendalloftheothersessionsatthisconference!